5-HT7 receptor deletion enhances REM sleep suppression induced by selective serotonin reuptake inhibitors, but not by direct stimulation of 5-HT1A receptor.
5-HT(7) receptors are involved in REM sleep and possibly in mood disorders. REM sleep suppression and antidepressant-like behavior is observed in 5-HT(7)(-/-) mice and in rats treated with 5-HT(7) receptor antagonists. We recently demonstrated that pharmacological blockade of 5-HT(7) receptors enhances REM sleep suppression and antidepressant-like behavior induced by citalopram in rodents. It has been hypothesized that the effect of citalopram on sleep is essentially mediated by the activation of 5-HT(1A) receptors. The present study investigates the impact of 5-HT(7) receptor gene deletion on the effect of various reuptake inhibitors on REM sleep and probes the role of 5-HT(1A) receptors in this response. Three SSRIs (citalopram, fluoxetine and paroxetine) but not the tricyclic antidepressant desipramine had a significantly stronger REM sleep suppressive effect in 5-HT(7)(-/-) mice compared to 5-HT(7)(+/+) mice. In contrast, REM sleep was similarly reduced in 5-HT(7)(+/+) mice and 5-HT(7)(-/-) mice after treatment with the 5-HT(1A) receptor agonist ipsapirone. Furthermore, both 5-HT(7)(+/+) and 5-HT(7)(-/-) mice displayed the same increase in REM sleep duration produced by the 5-HT(1A) receptor antagonist WAY-100635. These findings indicate that 5-HT(7) receptor deletion augments the effect of various SSRIs on REM sleep suppression and that this effect is distinct from those mediated via 5-HT(1A) receptors.
Shelton
Jonathan
J
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Neuroscience, 3210 Merryfield Row, San Diego, CA 92121, USA. jshelto5@its.jnj.com
Bonaventure
Pascal
P
Li
Xiaorong
X
Yun
Sujin
S
Lovenberg
Timothy
T
Dugovic
Christine
C
D000704:Analysis of Variance; D000818:Animals; D004569:Electroencephalography / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011743:Pyrimidines / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D044282:Receptor, Serotonin, 5-HT1A / Q000172:deficiency / Q000502:physiology*; D011985:Receptors, Serotonin / Q000172:deficiency* / Q000235:genetics; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012895:Sleep, REM / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors
D011743:Pyrimidines; D044282:Receptor, Serotonin, 5-HT1A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C104425:serotonin 7 receptor; C043077:ipsapirone